Enthesitis-Related Arthritis (ERA)

Definition And ILAR Classification Criteria

Juvenile-onset spondyloarthritis characterized by inflammation of joints and entheses.
Accounts for 10-20% of juvenile idiopathic arthritis (JIA) cases globally, reaching up to 35% in Indian populations.

Primary Requirement	Plus Minimum Two Secondary Features (If both Arthritis and Enthesitis not present)	Exclusion Criteria
Arthritis AND Enthesitis	Sacroiliac tenderness or inflammatory lumbosacral pain	Psoriasis in patient or first-degree relative
OR	HLA-B27 antigen positivity	Systemic JIA features
Arthritis OR Enthesitis	Arthritis onset in male older than 6 years	Positive IgM rheumatoid factor (RF)
	Acute symptomatic anterior uveitis
	First-degree relative with HLA-B27 associated disease (ankylosing spondylitis, reactive arthritis, inflammatory bowel disease)

Predominantly affects males (male:female ratio 3.4:1 to 7:1).
Mean age at onset 10-13 years.
Strong genetic association with HLA-B27 antigen, positive in 50-90% of patients.
Pathogenesis involves IL-23/IL-17 pathway activation.
Arthritogenic peptide hypothesis suggests HLA-B27 presents joint-specific peptides to autoreactive T-cells mimicking enteric bacteria (Salmonella, Shigella).
Misfolding hypothesis proposes HLA-B27 heavy chains accumulate in endoplasmic reticulum initiating pro-inflammatory stress response.

Insidious onset with intermittent musculoskeletal pain and stiffness.
Asymmetric oligoarthritis predominantly involving large joints of lower extremities (knees, ankles, hips).
Midfoot arthritis (tarsitis) highly specific, causing profound pain and swelling.
Hip involvement frequent at presentation, marking poor prognosis.

Exquisite point tenderness at tendon, ligament, or fascia insertion sites.
Most frequent sites: Achilles tendon insertion, plantar fascia insertion on calcaneus.
Knee sites: Tibial tuberosity, superior and inferior poles of patella (2, 6, 10 o'clock positions).

Develops progressively, initially presenting as inflammatory back pain.
Pain worsens with rest, awakens patient at night, improves with exercise.
Sacroiliitis elicited by pelvic compression or sacroiliac distraction.
Restricted thoracolumbar mobility assessed via modified Schober test (expansion <5 cm).

Acute symptomatic anterior uveitis: Presents with red, painful eye, photophobia, blurred vision.
Uveitis typically unilateral, recurrent, resolving without long-term damage.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) normal to moderately elevated.
HLA-B27 testing highly supportive, tested via flow cytometry or polymerase chain reaction.
Antinuclear antibodies (ANA) and rheumatoid factor (RF) consistently negative.

Magnetic resonance imaging (MRI) remains gold standard for early detection.
MRI pelvis with contrast detects active sacroiliitis, demonstrating bone marrow edema, osteitis, capsulitis.
Ultrasound localizes structural enthesopathy, increased vascularity, soft tissue swelling.
Conventional radiographs show late irreversible changes: joint space narrowing, subchondral sclerosis, syndesmophyte formation (bamboo spine).

Non-steroidal anti-inflammatory drugs (NSAIDs): First-line therapy for symptomatic relief of arthritis and enthesitis (Naproxen, Indomethacin).
Intra-articular corticosteroid injections: Triamcinolone hexacetonide targeted for isolated peripheral joint flares.
Conventional synthetic DMARDs (csDMARDs): Sulfasalazine (40-50 mg/kg/day) preferred over methotrexate for peripheral arthritis and enthesitis. Methotrexate ineffective for axial disease.
Biologic DMARDs (bDMARDs): Tumor necrosis factor (TNF) inhibitors (Adalimumab, Etanercept) mandated for active sacroiliitis, axial disease, or refractory peripheral arthritis.
Adalimumab preferred over etanercept if associated uveitis present.

Aggressive physical therapy preventing flexion contractures and postural deformities.
Deep breathing exercises maintaining chest expansion.
Custom orthotics alleviating focal entheseal pain.

Exhibits poorer long-term outcome compared to oligoarticular JIA.
High risk of progression to ankylosing spondylitis in adulthood.
Complications include fixed flexion deformities, severe hip joint destruction requiring arthroplasty, atlantoaxial subluxation.